Percutaneous electrode array

ABSTRACT

A percutaneous electrode array is disclosed for applying therapeutic electrical energy to a treatment site in the body of a patient. The array comprises a plurality of electrode microstructures which are inserted into the epidermis, thereby overcoming the inherent electrical impedance of the outer skin layers and obviating the need to prepare the skin surface prior to an electro-therapy treatment. The array preferably includes an adhesion layer to help keep the electrode microstructures inserted into the epidermis during the duration of the therapeutic treatment, and temperature and condition monitoring devices to ensure proper treatment and enhance patient safety.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This is a continuation-in-part of U.S. application Ser. No.09/756,999, filed Jan. 8, 2001, now U.S. Pat. No.______, which claimspriority to U.S. provisional application No. 60/175,003, filed on Jan.7, 2000 and also to U.S. provisional application No. 60/183,258, filedon Feb. 17, 2000, each of which is hereby incorporated by reference foreach of its teachings and embodiments.

FIELD OF THE INVENTION

[0002] This invention relates to an electro-therapy method and apparatusand more particularly to a method and apparatus for applying atherapeutic electrical signal for relieving pain arising from temporaryor chronic conditions or during or after surgery.

BACKGROUND OF THE INVENTION

[0003] Electro-therapy is the application of electrical energy to thebody of a human patient to provide a therapeutic effect. The therapeuticeffects produced by electro-therapy include the blockage of pain,residual pain relief possibly due to the release of endorphins or otheropiate-like analogs, relief from headache pain, increase of blood flow,increases in the range of motion, cartilage regrowth or regeneration,accelerated bone growth, electronic epidural for childbirth and otherbeneficial effects that result from the introduction of a low frequencyelectric field into tissue beneath the skin. Electro-therapy as definedby this application does not include electro-osmosis, electroporation,or iontophoresis, or any other process in which electrical energy suchas an electrical field or electric currents are used to promote thetransdermal transportation of chemicals or fluids into or out of thebody. Nor does it include electrosurgery where radiofrequency electricalenergy is used to cut or cauterize tissue.

[0004] Electro-therapy typically employs a non-invasive technique tointroduce the electrical energy into the patient's body. Disposableelectrode pads are placed on the epidermal surface of a patient andcoupled to an electric generator. The generator supplies two or moreoscillating or complex morphology electric currents to a patient, withrespective selected electrode pads separated from one another on thepatient's body with a pain site located between the electrode pads withthe majority of the electric field positioned perpendicular to each skinsurface on which the pads reside. The electric currents have frequenciesof at least about 1 KHz and differing by as little as 1 Hz up to about250 Hz from each other. A non-linear action of nerve fiber membranesand/or other electrochemically-active structures or fluids causes amixing of the two independent frequency signals in a volume of tissuesurrounding and beneath the pads along an axis between them to produce atherapeutic effect. The mixing yields a distribution of synthesized sumand difference frequencies among which is a therapeutic low frequencyequivalent to a beat frequency of the signals.

[0005] In order to penetrate the tissue beneath the skin and provide atherapeutic effect, electrical signals applied to the body must overcomethe electrical impedance of the skin. Electrical impedance is a propertyof the skin that limits the amount of current that can pass through theskin. The top layer of the skin, the stratum corneum, is made up of deadskin cells and contributes to the skin's high electrical impedance. Dry,intact skin can have an impedance which exceeds a hundred thousand ohms.Even carefully prepared skin, i.e., where the hair has been shaved orotherwise removed, where debridement of devitalized or contaminatedtissue has been performed, and where the skin's surface has beenmoisturized, can still have an impedance of over one thousand ohms. Apotentially large voltage would be necessary to overcome the skinimpedance and drive a therapeutically useful amount of electricalcurrent through body tissues. The relatively large amount of energyrequired limits the amount of time that a portable generator devicepowered by batteries can be used.

[0006] Additionally, electrical currents may travel across or justbeneath the surface of the skin, further reducing the amount of usefulcurrent provided to body tissues. This leakage current arises from thevarious layers of skin, and can limit the range of frequencies that canbe applied to body structures. The skin layers contribute electricalcapacitance and resistive properties which act as a barrier to currentflow, thus requiring a larger power source to compensate for the leakagecurrent, further limiting battery lifetime.

[0007] Biomedical studies conducted in other unrelated fields havedetermined ways to reduce skin impedance. For example, one studyinvolved the use of a silicon micro-needle array to evaluatelarge-molecule transportation properties of the array/skin interface(See Henry, S. et al., “Microfabricated Microneedles: A Novel Approachto Transdermal Drug Delivery,” 87 J. Pharm. Sci. 922-925 (1998)). Amicro-needle array is an array of small injection needles having alimited length so that a sufficient quantity of drugs can be injectedthough the needles into the skin, without the accompanying painperceived by the patient as with a standard injection needle. Volunteersdescribed the sensation of a micro-needle array insertion as beingsimilar to affixing a piece of tape to the skin. This study showed thatthe micro-needle array caused a 50-fold drop in skin resistance.

[0008] In another study, an array of silver or silver with silverchloride coated spikes were used as electrodes forelectroencephalography (EEG), i.e., the measurement of electricalactivity of the brain. (See Griss, P. et al., “Characterization ofMicromachined Spiked Biopotential Electrodes,” 49 IEEE Trans. Biomed.Eng. 597-604 (2002)). The array was applied to the forehead of thepatient to monitor EEG activity. The array was used to overcome skinresistance in order to detect the weak EEG electrical signals producedby the brain.

[0009] In addition, patents have been granted for needle arrays used inconjunction with iontophoresis and electroporation. In iontophoresis,and electric field is used to accelerate ionized molecules for additionto or removal from the body. For example, Gartstein et al. disclose intheir U.S. Pat. No. 6,379,324 issued on Apr. 30, 2002 a molded or castplastic micro-needle array in combination with an anode and cathodeelectrodes. Ionized drugs are accelerated into the body due to theapplied electric potential. Additionally, the array uses an electricfield to remove fluid from the body for analysis by a biologicalelectrochemical sensor.

[0010] In electroporation, short pulses of high electric fields areapplied to the cells causing the cell wall to transiently become porous.The applied electric field is adjusted to ensure that permanent damageto the cell wall does not result. Dev et al. disclose in their U.S. Pat.No. 6,451,002 issued on Sep. 17, 2002 a method for the treatment oftumors using an array of needles. High amplitude electrical signals areapplied to the needles that cause electroporation of the tissue cellsbetween the needles. Drugs used to treat the tumor are injected throughthe needles contemporaneously with the electroporation, therebyincreasing their introduction into the tissue cells.

[0011] Electrosurgery is the use of electrical radio frequency energy tocut tissue and coagulate bleeding during surgery. In such a procedure,the electrical energy is delivered to the patient through a probe. Theprobe permits the physician to direct the electrical energy to the areasof the patient's body that she wishes to cut. In order to complete theelectrical circuit, a return electrode is applied to the patient. Thereturn electrode employs a large surface area contacting the patient toreduce the current density and prevent burning of the patient's skin atthe return electrode. For example, Fleenor et al. disclose in their U.S.Pat. No. 6,544,258 issued Apr. 8, 2003 a self-regulating andself-limiting electrosurgical return electrode pad. A patient lies downon top of the pad during an electrosurgical procedure. The pad has alarge surface area designed to prevent high current densities andtemperature rise, thereby preventing patient trauma.

[0012] Electrode pads designed for use with medical test procedures suchas electrocardiograms (ECGs) typically employ an electrical conductor,such as a lead wire, electrically connected to an electrolyte disposedwithin the electrode pad. For example, Cartmell et al. discloses intheir U.S. Pat. No. 4,699,679 issued on Oct. 13, 1987 a disposablemedical electrode pad that includes two foam sheets with electricallyconductive adhesive layers on their lower surfaces. The pad furtherincludes an electrolyte gel matrix between the foam sheets. These padsare designed for monitoring electrical signals produced by the patient,but are sometimes used to apply stimulation signals to a patent, such asin electro-therapy.

[0013] It is known in the art that applying electrical energy to theskin can reduce the impedance of the skin. For example, Carim et al.discloses in their U.S. Pat. No. 6,032,060 issued on Feb. 29, 2000directing electrical energy through a medical electrode placed on theskin of the patient in order to electrically condition the skin. Thereduction in skin impedance increases the ability to monitor bioelectricsignals and can reduce the amount of energy necessary forelectroporation or transdermal iontophoresis.

[0014] Each of the above references provide and devices are designed forsensing electrical signals generated by the body, for deliveringpharmaceuticals to the body, or for performing electrical surgery on thebody. These devices disclosed by the references have physicalcharacteristics and electrical properties which make them suitable fortheir intended uses; however, they are not designed for electro-therapy.

SUMMARY OF THE INVENTION

[0015] A percutaneous electrode array is disclosed for applyingtherapeutic electrical energy to a treatment site in the body of apatient. The array comprises a plurality of electrode microstructureswhich are inserted into the epidermis, thereby overcoming the inherentelectrical impedance of the outer skin layers and obviating the need toprepare the skin surface prior to an electro-therapy treatment. Thearray preferably includes an adhesion layer to help keep the electrodemicrostructures inserted into the epidermis during the duration of thetherapeutic treatment, and temperature and condition monitoring devicesto ensure proper treatment and enhance patient safety.

[0016] In one aspect, the present invention is directed to apercutaneous electrode array for delivering therapeutic electricalenergy to a patient, comprising: a substrate having a top side and abottom side; and a plurality of electrodes each having a proximal end, adistal end, an axis from the proximal end to the distal end, and alength along the axis, wherein each electrode is attached to the topside of the substrate; wherein the electrodes have a total surface areaof more than 0.2 square centimeters.

[0017] In another aspect of the present invention, the electrodes aresubstantially a cylinder and have a diameter of 20 to 250 micrometers.

[0018] In another aspect of the present invention, the electrodes aresubstantially a rectangular parallelepiped having a pair of narrowsides, a pair of wide sides, a top side and a bottom side, and whereinthe wide sides have a width of 20 to 250 micrometers.

[0019] In another aspect of the present invention, the wide sides have awidth of about 200 micrometers.

[0020] In another aspect of the present invention, the length of theelectrodes is between 120 and 500 micrometers.

[0021] In another aspect of the present invention, the length of theelectrodes is between 150 and 200 micrometers.

[0022] In another aspect of the present invention, the distal end ofeach electrode is one or more of thinned and pointed to facilitateplacement into skin.

[0023] In another aspect of the present invention, the axis of theelectrodes is perpendicular to the substrate.

[0024] In another aspect of the present invention, the axis of theelectrodes is angled between perpendicular and parallel to thesubstrate.

[0025] In another aspect of the present invention, the substratecomprises a shape-memory metal alloy.

[0026] In another aspect of the present invention, the electrodescomprise one or more of doped semiconductor material, silicon-metalcompound, stainless steel, conductive polymer, carbon allotrope, and aconductive metal either in bulk or deposited material.

[0027] In another aspect of the present invention, a temperature elementis bonded to the substrate.

[0028] In another aspect of the present invention, the temperatureelement is one of a thermistor, a diode, a semiconductor junction, and athermocouple.

[0029] In another aspect of the present invention, the array furthercomprises an adhesion layer.

[0030] In another aspect of the present invention, the array furthercomprises a plurality of voids that pass through the top side of thesubstrate to the bottom side; and an adhesion layer comprising a bottomside, a top side, and a plurality of protrusions extending above the topside; wherein the top side of the adhesion layer is attached to thebottom side of the substrate, and the protrusions pass through the voidsto a first height above the top side of the substrate.

[0031] In another aspect of the present invention, the electrodes extendabove the first height of the adhesion layer between 150 and 200micrometers.

[0032] In another aspect of the present invention, the electrodes have atotal surface area above the first height of the adhesion layer of atleast 0.2 square centimeters.

[0033] In another aspect of the present invention, the adhesion layercomprises an electrically conductive hydrogel.

[0034] In another aspect of the present invention, the adhesion layercomprises a removable medical adhesive.

[0035] In another aspect of the present invention, the adhesion layerchanges color as a function of ambient conditions.

[0036] In another aspect of the present invention, the array furthercomprises a capacitive plate disposed on the bottom side of the adhesionlayer and an electrically insulating layer disposed on the capacitiveplate opposite the adhesion layer.

[0037] In another aspect of the present invention, the array furthercomprises a temperature element embedded in the adhesion layer.

[0038] In another aspect, the present invention is directed to apercutaneous electrode array for delivering therapeutic electricalenergy to a patient, comprising: a substrate having a top side and abottom side; and a plurality of electrodes each having a proximal end, adistal end, an axis from the proximal end to the distal end, and alength along the axis, wherein each electrode is attached to the topside of the substrate, the substrate has a surface area of greater than14.1 square millimeters and the electrodes have a total surface area ofless than 0.2 square centimeters.

[0039] In another aspect, the present invention is directed to anelectrode for delivering therapeutic electrical energy to a patient,comprising: a substrate having a first side and a second side; anadhesion layer comprising a bottom side and a top side attached to thefirst side of the substrate; a capacitive plate disposed on the bottomside of the adhesion layer; and an electrically insulating layerdisposed on the capacitive plate opposite the adhesion layer.

[0040] In another aspect, the present invention is directed to anelectrode for delivering therapeutic electrical energy to a patient,comprising: a substrate having a first side and a second side; and atemperature element bonded to the substrate.

[0041] In another aspect, the present invention is directed to a methodof producing a percutaneous electrode array comprising: micromachining amaster mold of a percutaneous electrode array having a substrate and aplurality of electrodes from silicon using semiconductor lithographicprocessing; creating a replica mold by electroplating thin film silverfollowed by nickel onto the master mold; heating, softening, and rollinga polymeric film; forcing the film into the replica mold using pressureto form an array structure; and cooling the array structure and removingthe structure from the replica mold.

[0042] In another aspect of the present invention, the method furthercomprises thermally processing array material to form a carbonizedstructure; and depositing an adhesive layer on the structure.

[0043] In another aspect of the present invention, the polymeric filmcomprises polymethyl methacrylate.

[0044] In another aspect of the present invention, the method furthercomprises spraying conductive inks onto the structure and heating thestructure to form a conductive coating.

[0045] In another aspect of the present invention, the method furthercomprises spraying, dipping or spin coating an indium tin oxideprecursor onto the array structure; and heating the structure to form aconductive film coating.

[0046] In another aspect of the present invention, the method furthercomprises forming a conductive film comprising indium tin oxide byevaporation or sputtering processes onto the array structure.

[0047] In another aspect, the present invention is directed to a methodof introducing therapeutic electrical energy to body tissues in atreatment site beneath the epidermis of a patient, comprising: providingan electro-therapy apparatus comprising: a signal generator configuredto produce first and second signals; and a first and second percutaneouselectrode array; positioning the first array on a first portion of thepatient's body and positioning the second array on a second portion ofthe patient's body such that the first and second arrays are positionedon the tissue of the patient, and the treatment site is located betweenthe first and second arrays; forming a therapeutic signal from saidfirst and second signals; and introducing the therapeutic signal throughthe first and second arrays.

BRIEF DESCRIPTION OF THE DRAWINGS

[0048]FIG. 1 is a side view of a percutaneous electrode array;

[0049]FIG. 2 is a cross-sectional view of human skin;

[0050]FIG. 3 is a side view of a percutaneous electrode array comprisingan adhesion layer;

[0051]FIG. 3A is an exemplary embodiment of a percutaneous electrodearray comprising a substrate with voids and an adhesion layer;

[0052]FIG. 3B is a top view of a percutaneous electrode array for usewith an adhesion layer;

[0053]FIG. 3C is a mechanical drawing illustrating an exemplaryembodiment of a percutaneous electrode array substrate and electrodes;

[0054]FIG. 4 is a side view of an electrode substrate and an adhesionlayer having an integrated capacitive element;

[0055]FIG. 5 is an exemplary circuit for measuring the capacitance ofthe capacitive element;

[0056]FIG. 6 is a side view of an electrode comprising an integratedthermal-sensing element;

[0057]FIG. 6A is a circuit diagram of an exemplary circuit that measuresthe temperature of an integrated thermistor;

[0058]FIG. 6B is a circuit diagram of an exemplary circuit that measuresthe temperature of an integrated semiconductor junction;

[0059]FIG. 6C is a circuit diagram of an exemplary circuit that measuresthe temperature of a thermocouple.

DETAILED DESCRIPTION OF THE INVENTION

[0060] The preferred embodiment disclosed provides for the applicationof therapeutic electrical signals to the body through a percutaneouselectrode array. The array efficiently delivers therapeutic electricalenergy into the body provided by an electro-therapy generator device. Anelectro-therapy generator device suitable for the production of suchenergy is described in U.S. patent application Ser. No. 09/756,999,entitled “Electro-Therapy Method and Apparatus,” filed on Jan. 8, 2001(and identified by Pennie & Edmonds attorney docket no. 9756-005-999),which is hereby incorporated by reference in its entirety for each ofits teachings and embodiments.

[0061] The configuration of a percutaneous electrode array is shown inFIG. 1. As shown in FIG. 1, the array comprises a substrate 110 and aplurality of electrodes 120. Electrodes 120 are attached to a top sideof substrate 110. An electrical connection to the array is made on thebottom side of substrate 110 and preferably the entire bottom surface ofthe array is protected with an insulating material, for example a wovenplastic or fabric cover.

[0062] Preferably, each electrode 120 comprises a rectangularparallelepiped attached at a proximal end to the substrate.Alternatively, each electrode 120 preferably comprises a cylinder orcone. The distal end of either electrode embodiment preferably furthercomprises one or more of a rounded triangular and pointed tip. The widthor diameter W1 of each electrode is preferably between 20 to 250micrometers.

[0063] The total surface area of the electrodes in the array equals thearea of each electrode times the number of electrodes in contact withthe skin. This area must be large enough to carry the electrical currentintroduced into the body by the electro-therapy generator device, whilelimiting the current density through the attached skin area. The surfacearea of each electrode comprises the area of the distal tip of theelectrode plus the surface area along the effective length of theelectrode, L1, i.e. the length that is inserted into the skin.Preferably, the total electrode surface area is greater than 0.2 squarecentimeters.

[0064] In an alternate preferred embodiment, the total electrode surfacearea is less than 0.2 square centimeters, but the substrate has asurface area greater than 14.1 square millimeters. The currentconducting area of the substrate in combination with the area of theelectrodes limits the current density to the skin.

[0065] The effective contact area of the electrodes is equal to thetotal surface area of the electrodes times a 56% reduction factor thataccounts for the electrode element surface area which comes in contactwith the body's ionic environment (70% of the electrode's length), andthe number of electrodes that are in contact with the skin (80% of thetotal number of electrodes in the array). The Food and DrugAdministration (FDA) currently limits the current density forelectro-therapy devices to less than 10 milliamps per square centimeterof contact area. One with skill in the art will recognize that severaldifferent configurations can be employed in order to achieve thenecessary effective contact area needed to reduce the current densitybelow the FDA limit. One way to increase the area is to increase thelength L1 of each electrode 120 in the percutaneous electrode array,i.e., the length in contact with the ionic environment of the body, inorder to maximize the area for electrical conduction. The maximum lengthis determined by observing the structure of the skin in the human body.

[0066]FIG. 2 illustrates a typical cross section of skin. The top layerof skin disclosed in FIG. 2, the stratum corneum, is comprised mostly ofdead skin cells. Other layers beneath the stratum corneum include thestratum lucidum, stratum granulosum, stratum spinosum and the stratumbasale. These five layers are collectively known as the epidermis. Theepidermis covers the germinating skin layers, known as the dermis, whichalso contains nerves, arteries, veins, or lymphatic vessels. Dependingon the location of the skin and its condition, the thickness of theepidermis is approximately 120 to 500 μm. The effective length ofelectrodes 120 is preferably between 120 and 500 μm, and more preferablybetween 150 and 200 μm so that the tip of electrode 120 penetrates intothe epidermis, but does not reach any nerves, arteries, veins, orlymphatic vessels. The effective length of the electrodes is preferablyadapted to the location where the array is attached and to the conditionof the skin within that region of body. The electrode length is tailoredto match these variables, enabling the electrode array to successfullytransit to a point just past the epidermis. This region is mostly devoidof pain receptors, making the insertion of the percutaneous electrodearray virtually painless. The elastic properties of the skin helps sealholes left behind by electrodes 120 after the array has been removed.Furthermore, the small diameter of each electrode 120, about thediameter of a typical human hair, will limit the amount of fluid thatcould flow through the hole created by the electrode.

[0067] The major axes of electrodes 120 are preferably perpendicular tosubstrate 110, but may be angled between perpendicular and parallel tothe substrate. Altering the mechanical properties of substrate 110and/or electrodes 120 may enhance adhesion of the array to the skin. Theelectrical contact integrity can be improved or maintained by increasingthe tension along the plane of substrate 110 between electrodes 120 andthe skin surrounding the region of penetration. For example, substrate110 may act as a spring. In this example, array 100 would be flexedprior to insertion. When array 100 is released, the tension stored insubstrate 110 would force electrodes 120 against the skin.

[0068] In an alternative preferred embodiment, array 100 comprises ashape-memory metal, e.g., Nitinol. The transition temperature of thealloy is preferably correlated with skin temperature by formulation andprocessing of the alloy. An array 100 made from such materials wouldpreferably expand or contract along a designated axis along the surfacearea of substrate 110. The expansion or contraction would forceelectrodes 120 laterally against the skin.

[0069] Electrodes 120 are preferably composed of material having goodelectrical conductive properties, such as doped silicon, silicon-metalcompounds, nickel/iron alloy, stainless steel, conductive inks, anallotrope of carbon such as glassy carbon derived from high carboncontent polymer pyrolysis, conductive polymers, polymer/graphite orpolymer/metal composite blends, and other biocompatible metals. Thematerials also have sufficient shear strength to prevent the fracture ofelectrodes in the skin. In the preferred embodiment, the array comprisestype 316 stainless steel.

[0070] As demonstrated above, the dimensions of the percutaneouselectrode array are extremely small. The development of such smallstructures are known in the art as micro electrical mechanical systems,or MEMS. MEMS is a multidisciplinary field encompassing microelectronicfabrication, polymerization techniques, physical chemistry, lifesciences and mechanical engineering. This cross-field environment hasled to the development of micro and nano-sized structures such asmicro-sensors, micro-motors and blood chemistry systems-on-a-chip. Themanufacture of some percutaneous electrode array embodiments may draw onknowledge from this field, as discussed below.

[0071] In an alternative preferred embodiment, glassy carbon electrodescan be made from any high carbon content polymer, such as pitch andpolyacrylonitrile. The material is formed into themicro-eletromechanical structures described above using the LIGAprocess. LIGA is a micromachining technology in which X-ray radiation isused in the production of high-aspect ratio, precision microstructures.LIGA parts are typically 2D extruded metal shapes, but 3D structures canbe created using this process. In the process, a master mold is createdfrom silicon using semiconductor lithographic processing. This mold isused to make replica molds by electroplating thin film silver followedby nickel. The replica mold has a thickness of 0.3 mm or greaterdepending on the mechanical loads borne by it. Next, polymeric materialis heated and softened and rolled into a film. The film is placedagainst the replica. Pressure is applied to force the polymeric materialinto the mold. After a short time period, the temperature is reduced andthe pressure removed.

[0072] Once the piece is formed, it is fired at 400 C to drive offvolatile chemicals and to thermoset the plastic. This is followed by an800 C bake in inert atmosphere to form carbonized material. The piece isfurther baked at about 1100 C to increase conductivity by forming agraphitic phase. Due to the small size of the electrodes, the relativelylow strain properties of the material do not present a breakage problem,even after many insertion cycles.

[0073] In an alternative preferred embodiment, conductive inks aresprayed onto the electrode array formed from a polymer such aspolymethyl methacrylate, or PMMA. Moderate heating to about 120 Cincreases both the conductivity and adhesion of the conductive film.

[0074] In another alternative preferred embodiment, indium tin oxide isapplied to a PMMA electrode array. A glycol-metal precursor of indiumtin oxide is sprayed or spin-coated onto the array and then heated toabout 400 C to form a conductive film coating. Indium tin oxide coatingsexhibit superb conductivity properties.

[0075] In another alternative preferred embodiment, a polymer blend isused to form the array. In such an array, a large amount of either metalpowder or graphite powder or graphite-nanofiber is added to a plasticprecursor to render the final material moderately conductive.Aggregation of high concentrations of the conductive material can leadto poor uniformity in the surface conductivity of the final compositedevice. Thermal processing of the composite, where some of the volatilecomponents of the mixture are driven off, may help to reduce thisdeleterious effect.

[0076] In another alternative preferred embodiment, pure metal iselectrodeposited on a master mold defining the electrode structure.Preferably, the metal has a conductivity between 100 and 10000 S/cm.

[0077] In an alternate embodiment, an adhesion layer is added to thearray to increase the conductivity of the array and adhere the array tothe skin. FIG. 3 illustrates a percutaneous electrode arrays thatincludes an adhesion layer. Array 300 comprises a substrate 310, aplurality of electrodes 320, and an adhesion layer 330. In a preferredmethod of manufacture, adhesion layer 330 is added to percutaneouselectrode array 300 by depositing material to form the layer on thesurface of substrate 310 between electrodes 320, or by piercing a sheetof layer material with array 300. Other methods may be evident to onewith skill in the art.

[0078] FIGS. 3A-3C illustrate a preferred embodiment of a percutaneouselectrode array that includes an adhesion layer. More specifically,array 300 illustrated in FIG. 3A comprises a substrate 310, a pluralityof electrodes 320, an adhesion layer 330, and a plurality of voids 340in substrate 310. Adhesion layer 330 is mounted to a rear side ofsubstrate 310 and protrudes through voids 340 in substrate 310. Adhesionlayer 330 secures the electrode to the patient, and preferably aids inthe conduction of the electrical signal into the body. Substrate 310provides support for adhesion layer 330.

[0079]FIG. 3B depicts a top view of array 300 before application ofadhesion layer 330. Electrodes 320 and voids 340 are arranged in a gridpattern. Preferably, array 300 is manufactured from a sheet of stainlesssteel stamped and/or etched to produce voids 340 and electrodes 320within the area of voids 340. Electrodes 320 are bended upward so thatthe major axis is in the desired direction, preferably normal to thesurface of substrate 310.

[0080]FIG. 3C is a mechanical drawing depicting an exemplary embodimentof percutaneous electrode array 300. The array comprises 3600 electrodesarranged in a regular grid pattern of 60 by 60. The width W1 of eachelectrode is approximately 200 um. A distance S1 of about 860 umseparates the electrodes. These dimensions result in a 5 cm by 5 cmarray of electrodes. Detail A shows the electrodes within the void areabefore they are bent upwards.

[0081] Suitable materials for use in layer 330 are a hydrogel or sol-gelconstruct containing an electrolyte. The minimum height of the hydrogellayer, H1, is limited by the estimated evaporation time and themechanical modulus of the gel. In a preferred embodiment, the arraycomprises a 635 um thick conductive gel, e.g. Uni-Patch type RG63B. Asthe hydrogel is exposed to the air, the water in the gel will evaporate,drying out the array and reducing the adhesive and conductive propertiesof the gel. The use of such an array would require a higher appliedvoltage. If the array is flexed or the skin/array mechanical interfaceis otherwise altered, an instantaneous drop in interfacial impedance canoccur, giving rise to an unpleasant feeling in the patient andconcentrating the current at points of good contact, raising thepossibility of a thermal burn. Adhesion layer 330 is preferably adaptedto provide an indication that the array is no longer suitable for use.

[0082] In a preferred embodiment, the hydrogel contains materials wellknown in the art that, when exposed to air after the packaging materialcontaining the electrode is opened, causes the hydrogel to slowly changecolor as a function of the evaporation rate. For example, the hydrogelmay have a normally clear appearance, but would turn into a dark colorafter exposure to the atmosphere. Alternatively, the normal appearanceof the hydrogel may be colored, and after exposure the hydrogel turnsclear. Such color changes indicate that the array needs to be replacedor that the integrity of the packaging is compromised and that the arrayis no longer sterile. In an alternate preferred embodiment, after thehydrogel has come into direct contact with human skin, a chemicalreaction would occur which changes the color of the hydrogel withoutleaving any residue on the skin.

[0083] In an alternative preferred embodiment, an adhesion layer of anelectrode is monitored to determine if the array has dried out or if thetemperature is increasing by measuring the electrical capacitance of theadhesion layer. FIG. 4 discloses the components of this embodiment. Asshown in FIG. 4, the electrode comprises a substrate 410, an adhesionlayer 430 and a capacitive plate 440 covered by an insulating layer 450.Capacitive plate 440 comprises a small section of conductive material onthe bottom side of adhesion layer 430, thus forming an electricalcapacitor comprising a dielectric (adhesion layer 430) between twoconductive plates (substrate 410 and plate 440). The capacitance of thearray capacitor is a function of both temperature and moisture content.An electrical lead is connected to plate 440 for connection in amonitoring circuit. Insulating layer 450 is coated over plate 440 toprevent plate 440 from electrically contacting the patient or others.

[0084] Circuits that measure capacitance are well known in the art. Anexemplary circuit for measuring the array capacitance is illustrated inFIG. 5. Measuring system 500 comprises a pair of identical low-passfilters 510, 520, a pair of low-offset comparators 530, 540, a flip-flop550, a binary counter 560, a microcontroller 570 and a high frequencyclock 580. A stable sinusoidal signal, a component of the signalgenerated by the electro-therapy generator device described in moredetail in U.S. patent application Ser. No. 09/756,999, entitled“Electro-Therapy Method and Apparatus,” filed on Jan. 8, 2001 (andidentified by Pennie & Edmonds attorney docket no. 9756-005-999), isused to determine the capacitance of adhesion layer 430.

[0085] Substrate 410 and capacitive plate 440 are connected to amonitoring circuit comprising low-pass filters 510, 520. Filters 510,520 preferably comprise 8-pole switched capacitor filters that pass astable sinusoidal signal. Comparators 530, 540, detect the zerocrossings of the stable sinusoidal output applied to the reference, afixed precision resistor, and the array capacitor. Reference comparator530 sets flip-flop 550, which starts counter 560, and capacitancecomparator 540 resets flip-flop 550, which stops counter 560. Highfrequency clock 580 provides a clocking signal to counter 560 whichincrements the counter once it is started. Counter 560 counts until thecapacitance signal performs its zero crossing. Microcontroller 570 readsthe count and then resets counter 560. Thus, counter 560 measures thetime difference between the zero crossings of the reference signal andthe current through the capacitor. Microcontroller 570 determines thephase shift between the signals from the count, which is indicative ofthe capacitance of the array capacitor. This measurement is independentof the amplitude of the two signals. Microcontroller 570 comprisesembedded software that uses this information to determine if the changein capacitance represents a fault state. If such a determination ismade, it can shut the system down and inform the user of the errorcondition. The software requires that a specific profile of the changein capacitance be maintained during system operation.

[0086]FIG. 6 discloses a preferred embodiment of an electrode comprisinga substrate 610 and a temperature-sensing element 640 bonded tosubstrate 610. The element comprises one of a thermistor, a diode, orother semiconductor junction, and a thermocouple. In a preferredembodiment, temperature element 640 is a small device, typically no morethan 0.5 mm in thickness. Temperature element 640 accurately measuresthe temperature of substrate 610.

[0087] In an alternative preferred embodiment, an electrode comprisingan adhesion layer has temperature-sensing element 640 embedded in theadhesion layer to monitor the integrity of the adhesion layer, forreasons stated above in the capacitance embodiment.

[0088]FIG. 6A is a circuit diagram of an exemplary circuit that measuresthe temperature of a percutaneous electrode array comprising anintegrated thermistor. In this embodiment, thermistor element 640 isconnected to a monitoring circuit comprising a voltage divider bridgecircuit 650, a differential amplifier 660, an analog-to-digitalconverter 670 and a microcontroller 680. Amplifier 660 eliminates anycommon mode noise associated with the lead length from the element 640to the monitoring circuit. The resultant voltage from amplifier 660varies as a function of array temperature. The monitoring circuitconverts the voltage signal to a binary value by analog-to-digitalconverter 670. The monitoring circuit further comprises microcontroller680 having software that converts the binary representation of thevoltage signal into the temperature of the array.

[0089]FIG. 6B is a circuit diagram of an exemplary circuit that measuresthe temperature of a percutaneous electrode array comprising either anintegrated semiconductor or discrete-device semiconductor junction. Inthis embodiment, element 640 comprises a diode or transistor having awell-characterized, temperature dependent behavior that measurestemperature to a high precision. As shown in FIG. 6B, the junction isconnected to a monitoring circuit comprising a constant current source651, a reference resistor 652, an amplifier 660, an analog-to-digitalconverter 670, and a microcontroller 680. The current is supplied tojunction 640 through resistor 652 to forward bias junction 640. Avoltage is measured across junction 640, which varies with junctiontemperature. The relationship between the junction voltage andtemperature is:

[0090] Vjunction=kT/q*ln(Ijunction/Ijunction saturation current), wherek is Boltzmann's constant (1.38×10⁻²³ J/K), T is the absolutetemperature in degrees Kelvin, q is the electron charge (1.601×10⁻¹⁹coulomb), Ijunction is the constant supplied reference current, andIjunction saturation current is the saturation current of thesemiconductor device (2×10⁻¹⁶ A for silicon).

[0091] Amplifier 660 increases the junction voltage to a useful leveland converter 670 transforms the signal into a binary representation.Microcontroller 680 uses the binary representation to determine thearray temperature.

[0092]FIG. 6C is a circuit diagram of an exemplary circuit that measuresthe temperature of a percutaneous electrode array comprising athermocouple. In this embodiment, temperature element 640 comprises athermocouple. A thermocouple is a device comprising two dissimilarmetals (e.g., platinum and rhodium) in electrical contact with eachother at a junction. The device generates an electromotive forcecorrelated to the temperature at the junction. The thermocouple requirescompensation for the temperature of the junctions formed between thedevice and its connecting leads (cold-junction compensation).

[0093] The monitoring circuit illustrated in FIG. 6C comprises anamplifier 660, a analog-to-digital converter 670 and a microcontroller.Amplifier 660 amplifies thermocouple 640's output voltage, converter 670converts it to a binary representation, and then software inmicrocontroller 680 uses the binary voltage value to determine thearray's temperature. Amplifier 660 contains the necessary components toeffect cold-junction compensation circuitry as is well known in the art.The software contains a lookup table as is well known in the art toconvert the binary representation of thermocouple voltage totemperature.

[0094] In a preferred embodiment, the measured temperature parameter isused as an interlock in the electro-therapy generator device to protectthe patient from harm. If for some reason the array rises above 40degrees Celsius, or ramps up in temperature at a higher rate than wouldnormally be expected, a temperature-monitoring portion of theelectro-therapy generator device can interrupt its output, thuslessening or eliminating the possibility of a bum or thermal irritation.Such detected conditions are used to inform the operator of potentialproblems with the integrity of the percutaneous electrode array, or theadhesion or placement of the array, two of the most likely causes of anincrease in current density.

[0095] In another embodiment, the electro-therapy generating devicecontinuously monitors the impedance of the percutaneous electrode array.The device includes a warning indicator which alerts the operator whenthe impedance of the percutaneous electrode array is too high,indicating that the array should be checked or replaced. The indicatorwould provide one or more of a visual indication, for example a blinkinglight emitting diode (LED) or an error message on an liquid crystaldisplay (LCD), an audio indication such as a beeping sound, and asensory indication such as a vibration producing device. The warningindicator can also be used to indicate error conditions such as a loosearray, unplugged lead wires, weak batteries, missing temperature signal,missing capacitance monitoring signal, or any other defective conditionof the array.

[0096] While the invention has been described with reference topreferred embodiments, it will be understood by those skilled in the artthat various changes may be made and equivalents may be substituted forelements thereof without departing from the scope of the invention. Inaddition, many modifications may be made to adapt a particular situationor material to the teachings of the invention without departing from theessential scope thereof. Therefore, it is intended that the inventionnot be limited to the particular embodiments disclosed as the best modecontemplated for this invention, but that the invention will include allembodiments falling within the scope of the appended claims.

What is claimed is:
 1. A percutaneous electrode array for deliveringtherapeutic electrical energy to a patient, comprising: a substratehaving a top side and a bottom side; and a plurality of electrodes eachhaving a proximal end, a distal end, an axis from the proximal end tothe distal end, and a length along the axis, wherein each electrode isattached to the top side of the substrate; wherein the electrodes have atotal surface area of more than 0.2 square centimeters.
 2. The array ofclaim 1, wherein the electrodes are substantially a cylinder and have adiameter of 20 to 250 micrometers.
 3. The array of claim 1, wherein theelectrodes are substantially a rectangular parallelepiped having a pairof narrow sides, a pair of wide sides, a top side and a bottom side, andwherein the wide sides have a width of 20 to 250 micrometers.
 4. Thearray of claim 3, wherein the wide sides have a width of about 200micrometers.
 5. The array of claim 1, wherein the length of theelectrodes is between 120 and 500 micrometers.
 6. The array of claim 1,wherein the length of the electrodes is between 150 and 200 micrometers.7. The array of claim 1, wherein the distal end of each electrode is oneor more of thinned and pointed to facilitate placement into skin.
 8. Thearray of claim 1, wherein the axis of the electrodes is perpendicular tothe substrate.
 9. The array of claim 1, wherein the axis of theelectrodes is angled between perpendicular and parallel to thesubstrate.
 10. The array of claim 1, wherein the substrate comprises ashape-memory metal alloy.
 11. The array of claim 1, wherein theelectrodes comprise one or more of doped semiconductor material,silicon-metal compound, stainless steel, conductive polymer, carbonallotrope, and a conductive metal either in bulk or deposited material.12. The array of claim 1, further comprising a temperature elementbonded to the substrate.
 13. The array of claim 12, wherein thetemperature element is one of a thermistor, a diode, a semiconductorjunction, and a thermocouple.
 14. The array of claim 1, furthercomprising an adhesion layer.
 15. The array of claim 1, furthercomprising: a plurality of voids that pass through the top side of thesubstrate to the bottom side; and an adhesion layer comprising a bottomside, a top side, and a plurality of protrusions extending above the topside; wherein the top side of the adhesion layer is attached to thebottom side of the substrate, and the protrusions pass through the voidsto a first height above the top side of the substrate.
 16. The array ofclaim 15, wherein the electrodes extend above the first height of theadhesion layer between 150 and 200 micrometers.
 17. The array of claim15, wherein the electrodes have a total surface area above the firstheight of the adhesion layer of at least 0.2 square centimeters.
 18. Thearray of claim 15, wherein the adhesion layer comprises an electricallyconductive hydrogel.
 19. The array of claim 15, wherein the adhesionlayer comprises a removable medical adhesive.
 20. The array of claim 15,wherein the adhesion layer changes color as a function of ambientconditions.
 21. The array of claim 15, further comprising a capacitiveplate disposed on the bottom side of the adhesion layer and anelectrically insulating layer disposed on the capacitive plate oppositethe adhesion layer.
 22. The array of claim 21, further comprising atemperature element embedded in the adhesion layer.
 23. A percutaneouselectrode array for delivering therapeutic electrical energy to apatient, comprising: a substrate having a top side and a bottom side;and a plurality of electrodes each having a proximal end, a distal end,an axis from the proximal end to the distal end, and a length along theaxis; wherein each electrode attached to the top side of the substrate,the substrate has a surface area of greater than 14.1 square millimetersand the electrodes have a total surface area of less than 0.2 squarecentimeters.
 24. An electrode for delivering therapeutic electricalenergy to a patient, comprising: a substrate having a first side and asecond side; an adhesion layer comprising a bottom side and a top sideattached to the first side of the substrate; a capacitive plate disposedon the bottom side of the adhesion layer; and an electrically insulatinglayer disposed on the capacitive plate opposite the adhesion layer. 25.An electrode for delivering therapeutic electrical energy to a patient,comprising: a substrate having a first side and a second side; and atemperature element bonded to the substrate.
 26. A method of producing apercutaneous electrode array comprising: micromachining a master mold ofa percutaneous electrode array having a substrate and a plurality ofelectrodes from silicon using semiconductor lithographic processing;creating a replica mold by electroplating thin film silver followed bynickel onto the master mold; heating, softening, and rolling a polymericfilm; forcing the film into the replica mold using pressure to form anarray structure; and cooling the array structure and removing thestructure from the replica mold.
 27. The method of claim 26, furthercomprising: thermally processing array material to form a carbonizedstructure; and depositing an adhesive layer on the structure.
 28. Themethod of claim 26, wherein the polymeric film comprises polymethylmethacrylate.
 29. The method of claim 26, further comprising sprayingconductive inks onto the structure and heating the structure to form aconductive coating.
 30. The method of claim 26, further comprisingspraying dipping or spin coating an indium tin oxide precursor onto thearray structure; and heating the structure to form a conductive filmcoating.
 31. The method of claim 26, further comprising forming aconductive film comprising indium tin oxide by evaporation or sputteringprocesses onto the array structure.
 32. A method of introducingtherapeutic electrical energy to body tissues in a treatment sitebeneath the epidermis of a patient, comprising: providing anelectro-therapy apparatus comprising: a signal generator configured toproduce first and second signals; and a first and second percutaneouselectrode array; positioning the first array on a first portion of thepatient's body and positioning the second array on a second portion ofthe patient's body such that the first and second arrays are positionedon the tissue of the patient, and the treatment site is located betweenthe first and second arrays; forming a therapeutic signal from saidfirst and second signals; and introducing the therapeutic signal throughthe first and second arrays.